Rit GTPase signaling promotes immature hippocampal neuronal survival

Weikang Cai, Shaun W. Carlson, Jennifer M. Brelsfoard, Catherine E. Mannon, Carole L. Moncman, Kathryn E. Saatman, Douglas A. Andres

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The molecular mechanisms governing the spontaneous recovery seen following brain injury remain elusive, but recent studies indicate that injury-induced stimulation of hippocampal neurogenesis contributes to the repair process. The therapeutic potential of endogenous neurogenesis is tempered by the demonstration that traumatic brain injury (TBI) results in the selective death of adult-born immature neurons, compromising the cell population poised to compensate for trauma-induced neuronal loss. Here, we identify the Ras-related GTPase, Rit, as a critical player in the survival of immature hippocampal neurons following brain injury. While Rit knock-out (Rit -/-) did not alter hippocampal development, hippocampal neural cultures derived from Rit -/-mice display increased cell death and blunted MAPK cascade activation in response to oxidative stress, without affecting BDNF-dependent signaling. When compared with wild-type hippocampal cultures, Rit loss rendered immature (Dcx +) neurons susceptible to oxidative damage, without altering the survival of neural progenitor (Nestin +) cells. Oxidative stress is a major contributor to neuronal cell death following brain injury. Consistent with the enhanced vulnerability of cultured Rit -/-immature neurons, Rit -/-mice exhibited a significantly greater loss of adult-born immature neurons within the dentate gyrus after TBI. In addition, post-TBI neuronal remodeling was blunted. Together, these data identify a new and unexpected role for Rit in injury-induced neurogenesis, functioning as a selective survival mechanism for immature hippocampal neurons within the subgranular zone of the dentate gyrus following TBI.

Original languageEnglish
Pages (from-to)9887-9897
Number of pages11
JournalJournal of Neuroscience
Volume32
Issue number29
DOIs
StatePublished - Jul 18 2012

ASJC Scopus subject areas

  • General Neuroscience

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